Microglia drive demyelination via multiple sclerosis antibodies and BTK signaling
Microglia are the predominant immune cells in multiple sclerosis (MS) demyelinating lesions, where they phagocytose myelin, but whether they destroy myelin or merely scavenge its debris is unknown. Here, we explore whether pathogenic autoantibodies found in MS may induce the phagocytic destruction of myelin by microglia. Applying patient-derived, myelin-targeting antibodies to the mouse cortex,…
Microglia, the primary immune cells in multiple sclerosis (MS) lesions, are known to engulf myelin, but the extent of their involvement in myelin destruction remains unclear. Researchers have now developed a new in vivo model of MS using patient-derived, myelin-targeting antibodies in mouse cortex. This model demonstrates that microglia encase intact myelin, leading to its loss.
By using two-photon microscopy, scientists observed the rapid envelopment of myelin by microglia, which is a key factor in myelin destruction. Single-cell RNA sequencing identified a unique signature of microglia associated with demyelination. Similarly, human MS lesions showed microglia enveloping intact myelin and the upregulation of similar genes.
Blocking a protein called Brutons tyrosine kinase (BTK) reduced microglial transcriptional changes and prevented myelin loss following microglial engulfment. This study provides strong evidence that microglia play a direct role in pathological myelin loss and suggests that BTK inhibition could be a promising therapeutic strategy to prevent demyelination by regulating microglia behavior.
Written by urgent.news from bioRxiv's reporting — not their text. Machine-written — may contain errors; check the original before relying on it.
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